We propose to understand the dynamics and control of the exchange of oxygen across the placenta, and its transport to the fetal tissues. This includes studies of the critical amount of placental diffusion required to maintain normal levels of oxygen in fetal blood, and in turn the relation of placental diffusing capacity to placental exchange area. We also will examine the effects of prolonged maternal hypoxia on maternal functions such as cardiac output, utero-placental blood flow and blood volume, and on placental diffusing capacity, as well as fetal functions such as weight, concentrations of several neurotransmitters, enzymes, and hormones. In addition, we will examine the factors which mediate these effects. We also are developing a mathematical model of the fetal circulation and oxygen delivery system, which embodies multiple large subsystems such as the kidney and regulation of body fluids, and the baroreceptor and chemoreceptor systems. This model is proving useful for predicting cardiovascular responses to stress as well as suggesting experiments to test the predictions. We also will explore both the short-term control of fetal blood pressure, blood volume, heart rate, and blood flow to several fetal organs, particularly the brain, heart, and adrenal glands. We also will examine the role of various substances such as the catecholamines, vasoactive peptides, the respiratory gases, other metabolites, and tissue factors in the regulation of blood flow to peripheral vascular beds in the fetus. In addition, we will examine the role of prolactin in affecting transplacental fluxes of water and several solutes, as well as explore prolactin's role in homeostasis of fetal fluid and blood volumes. Finally, we will investigate the relative role of concentrations of arterial O2, CO2, hydrogen ion, and arterial blood pressure in the control of blood flow to the fetal brain. Overall, these studies will lead to greater understanding of the control of the fetal cardiovascular oxygen delivery system.